The Helicobacter pylori virulence effector CagA abrogates human β-defensin 3 expression via inactivation of EGFR signaling
| Autor: | Carsten Holland, Thomas F. Meyer, Sina Bartfeld, Mirjana Kessler, Bianca Bauer, Ervinna Pang |
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| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
beta-Defensins Antimicrobial peptides Virulence Down-Regulation Gene Expression Protein Tyrosine Phosphatase Non-Receptor Type 11 Protein tyrosine phosphatase Biology Microbiology Cell Line Bacterial Proteins Virology Immunology and Microbiology(all) CagA Humans Defensin Pathogen Molecular Biology Immune Evasion Gene knockdown Antigens Bacterial Microbial Viability Helicobacter pylori Effector bacterial infections and mycoses ErbB Receptors Parasitology Signal Transduction |
| Zdroj: | Cell hostmicrobe. 11(6) |
| ISSN: | 1934-6069 |
| Popis: | SummaryAntimicrobial peptides are constituents of the first-line innate mucosal defense system that acts as a barrier to establishment of infection. The highly successful human gastric pathogen, Helicobacter pylori, is able to persistently colonize its host despite inducing expression of several antimicrobial peptides, including human β-defensin 3 (hBD3). We find that hBD3 is highly active against H. pylori in vitro and is rapidly induced during early infection via EGFR-dependent activation of MAP kinase and JAK/STAT signaling. However, during prolonged infection, hBD3 was subsequently downregulated by the H. pylori virulence determinant CagA. Upon translocation into host cells, CagA activated the cellular tyrosine phosphatase, SHP-2, terminating EGFR activation and downstream signaling and increasing bacterial viability. Chemical inhibition and knockdown of SHP-2 expression rescued hBD3 synthesis and bactericidal activity. Thus, we reveal how cagPAI-positive H. pylori strains use CagA to evade a key innate mucosal defense pathway to support the establishment of persistent infection. |
| Databáze: | OpenAIRE |
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